Oncotarget

Reviews:

Gene mutations and actionable genetic lesions in mantle cell lymphoma

Makhdum Ahmed, Leo Zhang, Krystle Nomie, Laura Lam and Michael Wang _

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Oncotarget. 2016; 7:58638-58648. https://doi.org/10.18632/oncotarget.10716

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Abstract

Makhdum Ahmed1,2, Leo Zhang1, Krystle Nomie1, Laura Lam1 and Michael Wang1

1 Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

2 The University of Texas Health Science Centre, Houston, Texas, USA

Correspondence to:

Michael Wang, email:

Keywords: MCL (mantle cell lymphoma), mutations, actionable genetic lesions, epigenetic, gene targets

Received: May 13, 2016 Accepted: July 01, 2016 Published: July 19, 2016

Abstract

Mutations and epigenetic alterations are key events in transforming normal cells to cancer cells. Mantle cell lymphoma (MCL), a non-Hodgkin’s lymphoma of the B-cell, is an aggressive malignancy with poor prognosis especially for those patients who are resistant to the frontline drugs. There is a great need to describe the molecular basis and mechanism of drug resistance in MCL to develop new strategies for treatment. We reviewed frequent somatic mutations and mutations involving the B-cell pathways in MCL and discussed clinical trials that attempted to disrupt these gene pathways and/or epigenetic events. Recurrent gene mutations were discussed in the light of prognostic and therapeutic opportunity and also the challenges of targeting these lesions. Mutations in the ATM, CCND1, TP53, MLL2, TRAF2 and NOTCH1 were most frequently encountered in mantle cell lymphoma. Translational models should be built that would assess mutations longitudinally to identify important compensatory, pro-survival and anti-apoptic pathways and actionable genetic targets.


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